This proposal for a Pittsburgh MIDAS Center of Excellence (U54) builds upon our proven track record of productivity in the NIGMS Modeling of Infectious Disease Agent Study MIDAS program. In that prior collaborative effort we successfully advanced both the theory and practice of epidemic modeling. We developed large scale agent-based simulations of a threatening avian influenza pandemic, used our models to evaluate potential epidemic control strategies, and advised the highest levels of the US Government and the WHO on public health policy. The senior investigators from our MIDAS team - Burke, Ferguson, and Epstein - constitute the nucleus of this proposed Center of Excellence. Research within the Center of Excellence is divided into seven project teams, each focusing on a specific component problem in computational modeling; all seven projects are complementary without duplication. Four of the projects (Parameters, Behavior, Evolution, and Environment) seek to model the dynamical processes and subprocesses of infectious disease epidemics, while three others (Decisions, Preparedness, Applied Modeling) seek to improve the utility of models in public health policy decision-making. A unique feature of this Center of Excellence is its exceptionally interdisciplinary character; there is vigorous participation of behavioral scientists, psychologists, lawyers, and public health practitioners, and there are strong collaborations with public health agencies at the county (Allegheny), state (Pennsylvania) and national (CDC) levels. Three cores (Administrative; Education, Training, & Outreach; Computing) provide support across the Center. Key personnel are drawn from the University of Pittsburgh, Carnegie Mellon University, the Pittsburgh Supercomputing Center, Johns Hopkins University, the Brookings Institution, and Imperial College, all outstanding research institutions. We are well positioned to provide continued leadership in the renewed MIDAS network, and we are deeply committed to collaborative research not only within our own Center of Excellence but across the entire MIDAS network structure.